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However, the short serum half\u2010life of TRAIL and lack of efficient in vivo administration approaches have largely hindered its clinical use. Using nanoparticles (NPs) as carriers in gene therapy is considered as an alternative approach to increase TRAIL delivery to tumors as transfected cells would be induced to secrete TRAIL into the tumor microenvironment. To enable effective delivery of plasmid DNA encoding <jats:italic>TRAIL<\/jats:italic> into glioblastoma (GBM), we developed a targeted iron oxide NP coated with chitosan\u2013polyethylene glycol\u2013polyethyleneimine copolymer and chlorotoxin (CTX) and evaluated its effect in delivering <jats:italic>TRAIL<\/jats:italic> in vitro and in vivo. NP\u2013TRAIL successfully delivers <jats:italic>TRAIL<\/jats:italic> into human T98G GBM cells and induces secretion of 40 pg mL<jats:sup>\u22121<\/jats:sup> of TRAIL in vitro. Transfected cells show threefold increased apoptosis as compared to the control DNA bound NPs. Systemic administration of NP\u2013TRAIL\u2013CTX to mice bearing T98G\u2010derived flank xenografts results in near\u2010zero tumor growth and induces apoptosis in tumor tissue. Our results suggest that NP\u2013TRAIL\u2013CTX can potentially serve as a targeted anticancer therapeutic for more efficient TRAIL delivery to GBM.<\/jats:p>","DOI":"10.1002\/adhm.201500563","type":"journal-article","created":{"date-parts":[[2015,10,26]],"date-time":"2015-10-26T03:09:27Z","timestamp":1445828967000},"page":"2719-2726","source":"Crossref","is-referenced-by-count":81,"title":["Nanoparticle\u2010Mediated Target Delivery of TRAIL as Gene Therapy for Glioblastoma"],"prefix":"10.1002","volume":"4","author":[{"given":"Kui","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Materials Science and Engineering University of Washington  Seattle WA 98195 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Forrest M.","family":"Kievit","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery University of Washington  Seattle WA 98195 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Jeon","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Engineering University of Washington  Seattle WA 98195 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Silber","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery University of Washington  Seattle WA 98195 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard G.","family":"Ellenbogen","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery University of Washington  Seattle WA 98195 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miqin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Engineering University of Washington  Seattle WA 98195 USA"},{"name":"Department of Neurological Surgery University of Washington  Seattle WA 98195 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,10,26]]},"reference":[{"key":"e_1_2_6_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.03.034"},{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043330"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2818"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.12.6242"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2277"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers5041271"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1769"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cgt.7700514"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5381.1322"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.2174\/156652305774964631"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2465"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc821"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(99)80034-9"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0806647106"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-09-0415"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(98)00409-8"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.25.1991"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI6926"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/5517"},{"key":"e_1_2_6_20_1","doi-asserted-by":"crossref","first-page":"3535","DOI":"10.1200\/jco.2007.25.18_suppl.3535","volume":"25","author":"Pan Y.","year":"2007","journal-title":"J. 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